The NINDS Stroke Trial Network (NSTN) has been charged with the development and testing of new therapies for stroke treatment, recovery/rehabilitation, and prevention that can decrease the global burden of stroke. The overall goal of this National Coordinating Center (NCC) application for the NSTN is to provide interdisciplinary leadership, expertise, innovation, and infra-structure for the efficient initiatin, completion, and dissemination of results of Phase I, II and III stroke trials, as well as biomarker-validation studies, as prioritized by the NSTN and NINDS leadership. Our NCC leadership team has extensive experience in initiating, directing, and completing large multi-center trials. The recent Stroke PRG and NINDS review of the SPOTRIAS program recognized the importance of a stroke-oriented clinical trial network, the growing collaboration among SPOTRIAS centers, and the need for similar networks for stroke recovery and prevention. However, in reality, there has been no organized coordinated approach to stroke trials in the U.S. As result, multiple NINDS- funded trials have directly competed against one another within the same treatment space at the same institutions, thereby slowing recruitment for all of the trials. Finally, entire trial infrastructures have been created and then dismantled with each large NINDS-funded Phase II and Phase III stroke trial; this has resulted in enormous inefficiency and increased costs in the evaluation of new treatments. Our Specific Aims for the NCC and the entire NSTN are: 1) create the NSTN infrastructure and initiate collaborative relationships within the NSTN and with the NETT, NeuroNext, ongoing NINDS-funded stroke trials, CTSAs, non-U.S. stroke networks, and industry. 2) Facilitate the design, oversight, and management of 6-8 Phase I to III clinical trials of acute treatment, recovery/rehabilitation, and prevention within the next five yers and meet recruitment goals by addressing recruitment barriers within the NSTN, collaborating with other NINDS-funded networks and non- U.S. stroke networks, and establishing a rigorous quality control process for monitoring recruitment, adherence to established deadlines, and protocol compliance to facilitate the overall success of the RCCs. 3) Implement network-wide educational activities and mentoring programs for NSTN fellows, faculty, and coordinators in collaboration with the NETT and NeuroNext networks.